FDA approves removal of black box warning for six menopausal hormone therapies

The FDA has approved drug label changes to six menopausal hormone replacement therapies (HRT), according to a recent news release. This was done to clarify risks for taking these drugs, specifically warnings for cardiovascular disease, breast cancer and probable dementia, all of which were removed.

This removal was initiated in November 2025 after a comprehensive review of the scientific literature. Twenty-nine drug companies have submitted proposed labeling changes at the FDA’s request. The first six drugs are:

1. Progesterone, USP capsules 100 mg and 200 mg (Prometrium) (progestogen alone)
2. Estradiol gel, for topical use (Divigel) (systemic estrogen alone)
3. Synthetic conjugated estrogens, A tablets for oral use (Cenestin) (systemic estrogen alone)
4. Synthetic conjugated estrogens, B tablets for oral use (Enjuvia) (systemic estrogen alone)
5. Estradiol vaginal system (Estring) (topical vaginal estrogen)
6. Estradiol and progesterone capsules for oral use (Bijuva) (systemic estrogen and progestogen)

“With today’s action, we are delivering on our promise to make sure women have accurate, scientifically grounded information about the potentially life-changing benefits of HRT,” FDA Commissioner Marty Makary, M.D., M.P.H., said in the news release. “Women face symptoms of menopause that can last for years, and our efforts will help these women make well-informed medical decisions.”

Hormone replacement therapy is an effective treatment to address menopause symptoms, such as hot flashes, mood swings and vaginal dryness. It works by replacing the hormones lost during this life transition.

However, results from the Women’s Health Initiative study, which was a 15-year study that began in 1991 to study the effects of hormone therapy to protect against heart disease, led to an overall decline in HRT use. Published in 2002, the results showed that women who take HRT have an increased risk of breast cancer. This led the FDA to place a black box label warning, the most severe warning, on estrogen products. Providers became less willing to prescribe HRT for menopause symptoms, and menopausal women became less interested in taking it. Specifically, HRT use rates fell from approximately 22% to 4%.

Years later, a reexamination of the study results revealed that there were flaws in the study. First, women ages 50 to 79 were grouped together, which is an unfair representation of the age of menopause, which begins around age 50 and typically lasts less than a decade. Second, the reanalysis also found that for women in their 50s, the benefits of estrogen therapy typically outweighed the risks. This discovery has led to an increased interest in removing the black box label.

“This decision reflects our commitment to follow the science wherever it leads and to correct course when the evidence demands it,” Health and Human Services Secretary Robert F. Kennedy, Jr., said in the news release. “By removing these boxed warnings, we ensure that women receive accurate information about hormone therapy—free from exaggeration or fear. A healthcare system worthy of public trust tells the truth, updates its guidance as science evolves, and respects women’s ability to make informed choices about their own health.”

Other studies have shown that HRT, when taken within 10 years of menopause onset, has a reduction in all-cause mortality and fractures.

The release ends with a statement encouraging women interested in beginning HRT to talk to their doctors. The official updated FDA drug labels are available here.